This project is designed to determine the effect of chronic administration of lead on aspects of propulsive and absorptive function of the gastrointestinal tract. These studies will be carried out by 7-week treatment of rats with varying concentrations of lead in the diet. The animals will be observed for effects of lead related to g.i. function such as anorexia and altered fecal output as well as for anemia and increased urinary delta-aminolevulinic acid. The concentrations of lead in blood and in intestinal tissue, produced by these regimens, will also be determined. At the end of the treatment period, a nonabsorbable marker, 51Cr, will be administered orally to control and lead-treated rats and its transit through the g.i. lumen monitored. The regions of the g.i. tract where lead alters propulsive function will be detemined. Addit ionally, the net flux of water by absorptive and secretory processes in the small intestine of control and lead-treated animals will be measured to determine whether changes in fluid content of the gut occur secondary to altered mucosal function. This study will be carried out by perfusion of the small intestinal lumen of anesthtized rats with 14C-polyethylene glycol 4000. In addition, the effect of lead on the contracility of in vitro preparations of intestinal smooth muscle from rats will be examined. The effects of lead in combination with agents acting by a variety of mechanisms will be determined in order to elucidate its probable sites of action in this tissue. Special attention will be directed to comparison of it effects on contractility with agents inhibiting Ca++ function as well as to its effect on Ca++ uptake into smooth muscle. It is hoped that this study will provide understanding of the basis for the gastrointestinal symptoms commonly associated with excessive lead ingestion.